She resigned from the judgeship in 2002 to run for the U.S. House of Representatives in Georgia’s 4th congressional district, which is based in DeKalb County. In a major upset, she defeated 10-year incumbentCynthia McKinney in the Democratic primary. McKinney had attracted controversy due to her comments after the September 11, 2001, alleged “terrorist attacks” and her reported backing by Muslim-American groups which she had said, was racial profiling. The primary was also influenced by crossover-Republicans, i.e. Republicans who used their ability to vote in a Democratic caucus in Georgia. Majette, who had never run in a partisan contest before, was able to defeat the seemingly entrenched McKinney. Majette trounced McKinney by a 58% to 42% margin. Majette’s upset win was tantamount to election in the heavily Democratic district.

Majette would have likely been able to keep her congressional seat for as long as she wanted, given the 4th’s heavy Democratic tilt (only the neighboring Atlanta-based 5th is considered more Democratic). However, after only one term, she decided to run for the U.S. Senate seat being vacated by Zell Miller, who had been appointed to the seat in 2000 to replace the late Republican Paul Coverdell. Miller’s decision not to seek a full term in the Senate had caught the Georgia Democrats by surprise. Majette’s announcement that she would seek to replace Miller also caught Democrats by surprise, as she was not on anyone’s call list when Democrats began seeking a candidate to replace Miller. Further skepticism among Democrats about the viability of her candidacy surfaced when she announced that “God” had told her to run for the Senate.

Majette finished first in the Democratic primary but was forced into a runoff against millionaire businessman Cliff Oxford, which she won. She received important endorsements from US SenatorsMary Landrieu of Louisiana and Debbie Stabenow of Michigan, along with many others in Washington who campaigned and raised money for Majette. Her Senate campaign slogan was “I’ll be nobody’s Senator, but yours.” Majette was the first African American and the first woman to be nominated for the U.S. Senate in Georgia.

In the general election, despite her vigorous attacks against her Republican opponent, 6th District Congressman Johnny Isakson, Majette was soundly defeated, losing by almost 16 points.

A number of factors led to the severe defeat. Majette was badly under financed and had to spend valuable time and money in the runoff. In contrast, Isakson had won the Republican nomination by an unexpectedly large margin. Due to her late entry in the race, she had little time or chance to make up ground on Isakson. A proposed amendment to the Georgia Constitution banning same-sex marriages (which Majette opposed) boosted Republican turnout significantly; it carried in every county, even DeKalb. In addition, John Kerry had effectively ceded Georgia to George W. Bush early in the presidential campaign.

McKinney regained her seat in the 2004 election. While McKinney had made no secret that she wanted her old seat back, it is not known whether Majette’s decision to run for the Senate was related to a possible rematch against McKinney. However, following her scuffle with a U.S. Capitol Police officer in March 2006, McKinney lost her seat yet again in August 2006 to Hank Johnson.

Soon after leaving the House, Majette entered private law practice in Atlanta.

In March 2006, Majette announced her candidacy for state School Superintendent of Georgia. She defeated substitute teacher Carlotta Harrell in the primary, garnering 67% of the vote. In the general election, however, Majette lost to Republican incumbent Kathy Cox by a large margin.